Exicorilant

Exicorilant (CORT 125281) is a selective and oral active glucocorticoid receptor (GR) antagonist, with a Ki value of 7 nM[1]. Exicorilant (CORT 125281) has potential to overcome adiposity, glucose intolerance and dyslipidaemia[2].

Research Areas >> Metabolic Disease

Signaling Pathways >> GPCR/G Protein >> Glucocorticoid Receptor

Ki: 7 nM (GR)[1].

Exicorilant (CORT 125281) reverses corticosterone-mediated GR activity in murine brown adipocytes in vitro[1].

Exicorilant (CORT 125281) reduces body weight, fat mass and plasma lipids in HFD-fed mice[2]. Exicorilant (CORT 125281) (6, 20 or 60 mg/kg/d, for 3 weeks in mice) at different dosages reduce body weight, fat mass, plasma TG, cholesterol and FFA in a dose-dependent manner, with no effect on lean mass[2]. Animal Model: Ten-week old male C57BL/6J mice HFD-fed[2]. Dosage: 6, 20, 60 mg/kg. Administration: Orally mixed with food daily for 3 weeks. Result: Reduced HFD-induced body weight gain with approximately 10% for CORT125281 at d21. Significantly lowered plasma TG (-56%) and cholesterol levels (-30%).

[1]. Hunt HJ, et al. Identification of the Clinical Candidate (R)-(1-(4-Fluorophenyl)-6-((1-methyl-1H-pyrazol-4-yl)sulfonyl)-4,4a,5,6,7,8-hexahydro-1H-pyrazolo[3,4-g]isoquinolin-4a-yl)(4-(trifluoromethyl)pyridin-2-yl)methanone (CORT125134): A Selective Glucocorticoid Receptor (GR) Antagonist. J Med Chem. 2017 Apr 27;60(8):3405-3421.

[2]. Kroon J, et al. Selective Glucocorticoid Receptor Antagonist CORT125281 Activates Brown Adipose Tissue and Alters Lipid Distribution in Male Mice. Endocrinology. 2018 Jan 1;159(1):535-546.